Infarction diseases, such as cerebral infarction and cardiac infarction, are caused by the formation of ischemic areas due to vascular occlusion or the like. In general, due to the formation of ischemic areas, oxygen and nutrients are not supplied to their surrounding areas. Further, simultaneously with or following this, inflammatory reactions and free radical formation occur to thereby expand necrotic areas for a short period of time. It is therefore very important, in the treatment of infarction diseases, to administer effective therapeutic agents in a relatively early stage after the development of ischemic areas.
Examples of known cerebral infarction therapeutic agents with internationally approved efficiency include thrombolytic agents (tissue plasminogen activators). However, thrombolytic agents must be administered within 4.5 hours after the formation of ischemic areas; thus, they cannot be used for patients for whom the time of formation of ischemic areas is completely unknown, or patients for whom 4.5 hours or more has already elapsed after the formation of ischemic areas. Edaravone is also known as another cerebral infarction therapeutic agent; however, it is necessary to administer this agent several times (generally twice a day).
In contrast, the present inventors report that RANKL protein inhibits proinflammatory cytokines, and has preventive and therapeutic effects on infarction diseases (PTL 1). In this case, the full length of RANKL protein is used as an active ingredient; however, it is preferable to use a shorter oligopeptide as an active ingredient, in terms of stability, economical efficiency, etc. However, it was not known which region of RANKL protein inhibited proinflammatory cytokines in cells (particularly microglial cells, macrophage cells, etc.), and had preventive and therapeutic effects on infarction diseases.